טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentSegal Vardit
SubjectProcesses at the Interface between Biomaterials and
Physiological Systems
DepartmentDepartment of Biomedical Engineering
Supervisors Professor Emeritus Noah Lotan
Professor Emeritus Uri Dinnar (Deceased)


Abstract

Metallic elements are widely used as blood-contacting biomaterials. Representative examples are heart valves and vascular stents. Yet, while they fulfill the mechanical requirements imposed, their biocompatibility is still to be improved.

Improving the biocompatibility of biomaterials may be carried out: (a) by a passive approach, where the surface is modified by covering it with more compatible materials; and (b) by an active approach, where the surface is covered with active agents capable to promote a desired biological effect.  However, none of these approaches lead yet to fully satisfactory results. The main problem associate with the existing approach of active biocompatibility is that one cannot maintain therapeutic doses of the active agent for the long period of time required .

This research was aimed mainly at improving the biocompatibility of metal-based implants by combining the passive and active approaches. Following the passive approach, films of organic components were deposited on the metal surface by electrochemical polymerization, which is a fast and convenient procedure. The active biocompatibility concept was implemented by immobilizing two enzymes (i.e. a-chymotrypsin and CuZn superoxide dismutase) within and on the electrochemically polymerized films covering the metal.  Immobilization of enzymes allows for their long time operation at the required site of action, where they act as a “local factory” for generating the desired products or eliminating unwanted materials.

It was found that: (a) Using appropriate monomers (e.g., pyrrole, tyramine), the metals were fully covered by an organic layer which prevents corrosion of and ion migration from the metal; (b) Enzymes were successfully immobilized within and on the films in an active form and retain activity for at least three months; (c)Immobilized a-chymotrypsin significantly decreases  the adsorption of proteins (e.g., radioactive- labeled fibrinogen).

Both the electrochemical polymerization and the immobilization of enzymes are non-specific procedures, and can be adapted to a wide range of polymers and enzymes, thus achieving the desired physiological effect.